The overall objective of Project 2 is to build upon our previous results using real time NMR imaging techniques that are optimally sensitive for the detection and characterization of normal and abnormal myocardial perfusion. Kinetic modeling of NMR contrast agents, developed in collaboration with investigators on Project 1, will be used to assess microscopic flow dynamics in the heart. Methods will be optimized in normal animals to clarify pertinent tracer kinetic assumptions. These include: 1) the quantitative relationship between the tissue concentration of agent and the NMR signal change, and 2) the ability of NMR to determine the arterial input function, and thus to extract quantitative information about RMBF based on tissue transit times. NMR determined flow values at rest and during high flow states will be validated using microsphere measurements of RMBF. Optimized RMBF techniques will then be used to measure the effect of coronary stenosis on these NMR parameters and to determine the utility of these methods in defining physiologically significant stenosis at rest and during pharmacological vasodilation. A new component of this research will study the NMR antibody imaging of irreversibly damaged myocardium. Monocrystilline iron oxide nanoparticles (MION) attached to antimyosin Fab fragments, developed by investigators on Project 5, will be characterized and evaluated in an infarction-reperfusion model. Finally, optimized NMR perfusion techniques in combination with MION-Fab imaging techniques will be used quantitatively to differentiate ischemic from infarcted myocardium.